Integrated strontium-rubidium radioisotope infusion systems

ABSTRACT

Methods for setting up, maintaining and operating a radiopharmaceutical infusion system, that includes a radioisotope generator, are facilitated by a computer of the system. The computer may include pre-programmed instructions and a computer interface, for interaction with a user of the system, for example, in order to track contained volumes of eluant and/or eluate, and/or to track time from completion of an elution performed by the system, and/or to calculate one or more system and/or injection parameters for quality control, and/or to perform purges of the system, and/or to facilitate diagnostic imaging.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/620,320, filed Jun. 12, 2017, which is a continuation of U.S. patentapplication Ser. No. 15/389,200, filed Dec. 22, 2016, now U.S. Pat. No.9,750,869, issued Sep. 5, 2017, which is a continuation of U.S. patentapplication Ser. No. 12/808,467, filed Jun. 16, 2010, now U.S. Pat. No.9,607,722, issued Mar. 28, 2017, which is a 371 National Stage ofInternational Application No. PCT/US09/47031, filed Jun. 11, 2009, whichin turn is a continuation of the following four patent applications:U.S. patent application Ser. No. 12/137,356, filed Jun. 11, 2008, nowU.S. Pat. No. 8,317,674, issued Nov. 27, 2012; U.S. patent applicationSer. No. 12/137,363, filed Jun. 11, 2008, now U.S. Pat. No. 7,862,534,issued Jan. 4, 2011; U.S. patent application Ser. No. 12/137,364, filedJune 11, 2008, now U.S. Pat. No. 9,597,053, issued Mar. 21, 2017; andU.S. patent application Ser. No. 12/137,377, filed Jun. 11, 2008, nowU.S. Pat. No. 8,708,352, issued Apr. 29, 2014. The entire contents ofall of these applications are incorporated herein by reference.

TECHNICAL FIELD

The present invention pertains to systems that generate and infuseradiopharmaceuticals, and, more particularly, to systems includingcomputer-facilitated maintenance and/or operation.

BACKGROUND

Nuclear medicine employs radioactive material for therapy and diagnosticimaging. Positron emission tomography (PET) is one type of diagnosticimaging, which utilizes doses of radiopharmaceuticals, for example,generated by elution within a radioisotope generator, that are injected,or infused into a patient. The infused dose of radiopharmaceutical isabsorbed by cells of a target organ, of the patient, and emitsradiation, which is detected by a PET scanner, in order to generate animage of the organ. An example of a radioactive isotope, which may beused for PET, is Rubidium-82 (produced by the decay of Strontium-82);and an example of a radioisotope generator, which yields a salinesolution of Rubidium-82, via elution, is the CardioGen-82® availablefrom Bracco Diagnostics Inc. (Princeton, N.J.). A PET scanner incombination with infused doses of radiopharmaceuticals may also beemployed to quantify blood flow rate, for example, through the coronaryarteries of a patient.

Set up, maintenance and operational procedures for infusion systems thatboth generate and inject doses of radiopharmaceuticals are relativelyinvolved in order to assure the safety and efficacy of each injecteddose for the patient. Efficiency in carrying out these procedures ishighly desirable for technical personnel, who work with these systems ona routine basis and would like to avoid unnecessarily prolonged exposureto radioactive radiation. Thus there is a need for new systemconfigurations that facilitate more efficient set up, maintenance andoperation.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings are illustrative of particular embodiments of thepresent invention and therefore do not limit the scope of the invention.The drawings are not to scale (unless so stated) and are intended foruse in conjunction with the explanations in the following detaileddescription. Embodiments of the present invention will hereinafter bedescribed in conjunction with the appended drawings, wherein likenumerals denote like elements.

FIG. 1A is a first perspective view of an infusion system, according tosome embodiments of the present invention.

FIG. 1B is another perspective view of a portion of a cabinet structureof the system shown in FIG. 1A, according to some embodiments.

FIG. 1C is a second perspective view of the system shown in FIG. 1A,according to some embodiments.

FIG. 1D is a schematic of an infusion circuit, according to someembodiments of the present invention.

FIG. 1E is a perspective view of exemplary sample vial shielding thatmay be employed in conjunction with the infusion system of FIG. 1A.

FIG. 2A is a perspective view of a shielding assembly for an infusionsystem, such as that shown in FIGS. 1A-C, according to some embodimentsof the present invention.

FIG. 2B is a perspective view of a framework of the system, according tosome embodiments, and FIG. 2B-1 is an enlarged detailed view of acomponent of the system, according to some embodiments.

FIG. 3A is another perspective view of the shielding assembly shown inFIG. 2A.

FIG. 3B is a perspective view of the infusion circuit, shown in FIG. 1C,configured and routed, according to some embodiments.

FIG. 3C is a perspective view of a disposable infusion circuitsubassembly, according to some embodiments.

FIG. 3D is a frame for the subassembly shown in FIG. 3C, according tosome embodiments.

FIG. 4 is a main menu screen shot from an interface of a computer, whichmay be included in systems of the present invention, according to someembodiments.

FIG. 5A is a schematic showing a first group of successive screen shotsfrom the computer interface, according to some embodiments.

FIG. 5B is a pair of screen shots from the computer interface, whichprovide indications related to eluant volume levels in a reservoir ofthe system, according to some embodiments.

FIG. 5C is a schematic showing a second group of successive screen shotsfrom the computer interface, according to some embodiments.

FIG. 6 is a schematic showing a third group of successive screen shotsfrom the computer interface, according to some embodiments.

FIGS. 7A-C are schematics showing a fourth group of successive screenshots from the computer interface, according to some embodiments.

FIGS. 8A-B are schematics showing a fifth group of successive screenshots from the computer interface, according to some embodiments.

FIGS. 9A-C are schematics showing a sixth group of successive screenshots from the computer interface, according to some embodiments.

FIG. 10 is a schematic showing a seventh group of successive screenshots from the computer interface, according to some embodiments.

FIG. 11 is an exemplary report which may be generated by the computerincluded in infusion systems, according to some embodiments.

FIGS. 12A-B are schematics of alternative infusion circuits that may beemployed by embodiments of the present invention.

FIG. 12C is a schematic illustrating exemplary activity profiles ofinjected doses of a radiopharmaceutical.

DETAILED DESCRIPTION

The following detailed description is exemplary in nature and is notintended to limit the scope, applicability, or configuration of theinvention in any way. Rather, the following description providespractical illustrations for implementing exemplary embodiments.Utilizing the teaching provided herein, those skilled in the art willrecognize that many of the examples have suitable alternatives that canbe utilized.

FIG. 1A is a first perspective view of an infusion system 10, accordingto some embodiments of the present invention, wherein system 10 is shownsupported by a cabinet structure, which includes a platform 113 (seenbetter in FIG. 2B) and a shell 13; shell 13 extends upward from a skirt11, that surrounds platform 113, to surround an interior space in whicha portion of infusion system 10 is contained (seen in FIG. 1C). Shell 13may be formed from panels of injection-molded polyurethane fittedtogether according to methods known to those skilled in the art. FIG. 1Aillustrates the cabinet structure of system 10 including a grip orhandle 14, which extends laterally from shell 13, in proximity to anupper surface 131 thereof, and a post 142, which extends upward fromshell 13, and to which a work surface, or tray 16 and a computer 17 are,preferably, attached, via an ergonomic, positionable mount. According tosome embodiments, computer 17 is coupled to a controller of system 10,which is mounted within the interior space surrounded by shell 13; and,a monitor 172 of computer 17 not only displays indications of systemoperation for a user of system 10, but also serves as a device for userinput (e.g. touch screen input). However, according to alternateembodiments, another type of user input device, known to those skilledin the art, may be employed by computer 17. Other types of user inputdevices may be included, for example, a keyboard, a series of controlbuttons or levers, a bar code reader (or other reader of encodedinformation), a scanner, a computer readable medium containing pertinentdata, etc. The user input device may be mounted on the cabinet structureof system 10, as shown, or may be tethered thereto; alternatively theuser input device may be remote from system 10, for example, located ina separate control room. According to some additional embodiments,another user input device, for example, in addition to a touch screen ofcomputer 17, may be remote from system 10 and used to start and stopinfusions, as well as to monitor system operation both during qualitycontrol infusions and during patient infusions. Operation of system 10,which is facilitated by computer 17, will be described below, inconjunction with FIGS. 4-9C.

FIG. 1A further illustrates two pairs of wheels 121, 122, mounted to anunderside of platform 113, to make system 10 mobile; handle 14 is shownlocated at an elevation suitable for a person to grasp in order tomaneuver system 10, from one location to another, upon pairs of wheels121, 122. According to some preferred embodiments, one or both pairs ofwheels 121, 122, are casters, allowing for rotation in a horizontalplane (swivel), in order to provide additional flexibility formaneuvering system 10 in relatively tight spaces.

FIG. 1B is a perspective view of a portion of system 10, on a side 111of the cabinet structure, which is in proximity to wheels 121, 122. FIG.1B illustrates a lever or pedal 125, which is located for activation bya foot of the person, who grasps handle 14 to maneuver system 10. In aneutral position, pedal 125 allows wheels 121, 122 to rotate, and, ifembodied as casters, to swivel freely. Pedal 125 may be depressed to afirst position which prevents a swiveling of wheels 121, 122, accordingto those embodiments in which wheels 121, 122 are casters, and may befurther depressed to brake wheels 121, 122 from rolling and swiveling,upon reaching a desired location. According to some embodiments, brakingmay be designed to slow system 10, for example, when rolling down anincline, and, according to yet further embodiments, system 10 mayinclude a motor to power movement thereof.

FIG. 1B further illustrates: a rear access panel 174 of shell 13, forexample, providing access to circuit boards of the aforementionedcontroller contained within the interior space that is surrounded byshell 13; an optional lock 184, to secure panel 174; a power jack 118,for connecting system 10 to a power source; and a printer 117 forproviding documentation of each patient infusion carried out by system10, and of system quality control test results. In some embodiments,system 10 may further include a power strip by which auxiliary equipmentmay be powered, and one or more additional electrical connectors, orports (not shown), which are supported by platform 113 and may beintegrated into shell 13, for example, in proximity to jack 118 orprinter 117; these electrical connectors/ports allow system 10 tocommunicate with, other devices used for nuclear imaging procedures, forexample, a PET scanner/camera, and/or for coupling to an intranetnetwork, and/or to the internet, for example, to link up with softwareprograms for various types of data analysis, and/or to link to computersof consulting clinicians/physicians, and/or to link into serviceproviders and/or component suppliers data bases for enhanced maintenanceand inventory management.

FIG. 1A further illustrates upper surface 131 of shell 13 includingseveral openings 133, 135, 139 formed therein. FIG. 1C is a partiallyexploded perspective view of system 10, wherein a removable access panel132 is shown as a contoured portion of upper surface 131, which, whenexposed, by lifting away a bin 18, that mates therewith, may be removedfrom another opening 137 formed in upper surface 131. FIG. 1C alsoprovides a better view of another panel 134 which may be lifted awayfrom opening 139. According to the illustrated embodiment, openings 139and 137 provide a user of system 10 with independent access to separateportions of infusion system 10, which are contained within shell 13, forexample, to set up and maintain system 10; and openings 133 and 135provide passageways for tubing lines to pass through shell 13. FIG. 1Cfurther illustrates an optional switch 102, which in case of anemergency, may be activated to abort function of system 10. Withreference to FIGS. 1A and 1C, it may be appreciated that an arrangementof features formed in upper surface 131 of shell 13, in conjunction withbin 18, tray 16 and computer 17, provide a relatively ergonomic andorganized work area for technical personnel who operate system 10.

Turning now to FIG. 1D, a schematic of an infusion circuit 300, whichmay be incorporated by system 10, is shown. FIG. 1D illustrates circuit300 generally divided into a first part 300A, which includes componentsmounted outside shell 13, and a second part 300B, which includescomponents mounted within the interior space surrounded by shell 13.(Parts 300A and 300B are delineated by dotted lines in FIG. 1D.) FIG. 1Dfurther illustrates second part 300B of circuit 300 including a portioncontained within a shielding assembly 200, which is designatedschematically as a dashed line. Some embodiments of shielding assembly200 will be described in greater detail, in conjunction with FIGS. 2A-Band 3A-B, below.

According to the illustrated embodiment, circuit 300 includes: an eluantreservoir 15, for example, a bag, bottle or other container, containingsaline as the eluant, which is shown hanging from a post, or hanger 141above upper surface 131 of shell 13 in FIG. 1A; a syringe pump 33, forpumping the eluant from reservoir 15, and a pressure syringe 34 (orother device or sensor), for monitoring pumping pressure; a filter 37,which may also serve as a bubble trap, for the pumped eluant; aradioisotope generator 21, through which the filtered eluant is pumpedto create a radioactive eluate, for example an eluate carryingRubidium-82 that is generated by the decay of Strontium-82, via elution,within a column of generator 21; and an activity detector 25, formeasuring the activity of the eluate discharged from generator 21, inorder to provide feedback for directing the flow of the eluate, via adivergence valve 35WP, either to a waste bottle 23 or through a patientline 305 p, for example, to inject a dose of the radiopharmaceuticaleluate into a patient. With reference back to FIG. 1A, patient line 305p is shown extending out from shell 13, through opening 135, to a distalend thereof, which, according to some embodiments, includes a filter.Patient line 305 p may be coupled to another line that includes apatient injection needle (not shown). Alternatively, patient line 305 pmay be coupled to another line (not shown), which extends from a sourceof another active substance, for example, a stress agent; the other lineis coupled to the line that includes the patient injection needle, inorder to permit injection of the additional active substance.

FIG. 1D illustrates an eluant tubing line 301 coupled to reservoir 15and to pump 33, and, with reference to FIGS. 1A-B, it may be appreciatedthat opening 133 provides the passageway for tubing line 301 to enterthe interior space surrounded by shell 13. According to some preferredembodiments, opening 133 includes a grommet-type seal that preventsleakage of eluant, which may spill from reservoir 15, into the interiorspace through opening 133, while allowing a user to assemble tubing line301 through opening 133. Likewise opening 135, which provides apassageway for patient line 305 p, may include a grommet-type seal.According to some embodiments, shell 13 further supports holders tosafely hold, for example, during transport of system 10, portions oftubing lines that extend outward therefrom, for example, line 301 and/orline 305 p.

FIG. 1D further illustrates another eluant tubing line 302 coupled topump 33 and a divergence valve 35BG, which may either direct pumpedeluant through a tubing line 304, to generator 21, or direct the pumpedeluant through a by-pass tubing line 303, directly to patient line 305p. Divergence valve 35BG, as well as divergence valve 35WP, whichdirects eluate from an eluate tubing line 305 either to a waste line 305w or to patient line 305 p, may each be automatically operated by acorresponding servomotor (not shown), coupled to the controller (notshown) of system 10, which controller receives feedback from activitydetector 25. When system 10 is operating for automatic infusion, todeliver a dose of radiopharmaceutical to a patient, for example,Rubidium-82 for diagnostic imaging, divergence valve 35BG is initiallyset to direct eluant to generator 21 and divergence valve 35WP is set todirect eluate from the generator into waste bottle 23, until activitydetector 25 detects the desired activity of the eluate, at which timethe feedback from activity detector 25 causes the controller to directthe corresponding servo-motor to re-set valve 35WP for diverting theflow of eluate into patient line 305 p. According to some embodiments,once a prescribed volume of the eluate has passed through patient line305 p, the controller directs the corresponding servomotor to re-setdivergence valve 35BG for diverting the flow of eluant through by-passline 303 and into patient line 305 p in order to flush, or push anyeluate remaining in patient line 305 p into the patient. According tosome embodiments, the controller may also direct the correspondingservomotor to re-set divergence valve 35WP back toward waste bottle 23,prior to the flush through by-pass line 303, in order to prevent backflow of eluant, through line 305, toward generator 21. According to somepreferred methods of operation, in certain situations, which will bedescribed in greater detail below, eluant is pumped through by-pass line303 immediately following the flow of the prescribed volume of eluateinto patient line 305 p, at a higher speed, in order to push the eluatein patient line 305, thereby increasing a flow rate of the injection ofeluate out from patient line 305 p and into the patient. For example,once the prescribed volume of eluate has flowed into patient line 305 p,and once divergence valve 35BG is set to divert flow through by-passline 303, the speed of pump 33 may be adjusted to increase the flow rateof eluant to between approximately 70 mL/min and approximately 100mL/min. This method for increasing the injection flow rate, isdesirable, if a relatively high flow rate is desired for patientinjection and a flow rate through generator 21 is limited, for example,to below approximately 70 mL/min, maximum (typical flow rate may beapproximately 50 mL/min), in order to avoid an excessive back pressurecreated by the column of generator 21 in upstream portions of tubingcircuit 300; the excessive back pressure could damage filter 37 orotherwise impede flow through eluant tubing line 302.

Although not shown in FIG. 1D, a number of sensors, for example, tomeasure pressure and/or flow velocity, may be incorporated into circuit300, according to some alternate embodiments, in order to monitor forflow anomalies, for example, related to occlusions/plugs in circuit 300and/or leaks, and/or to provide feedback for control of an activitylevel of infused doses of radiopharmaceutical. Suitable sensors for anyof the above purposes are known to those skilled in the art. Examples offlow meters that may be incorporated into circuit 300, include theInnova-Sonic® Model 205 Transit-Time Ultrasonic Liquid Flow Meter thatemploys digital signal processing (available from Sierra Instruments,Inc.) and the Flocat LA10-C differential pressure flow meter. Oneexample of a pressure sensor that may be employed to detect infusioncircuit occlusions is the PRO/Pressure-Occlusion Detector (availablefrom INTROTEK® of Edgewood, N.Y., a subsidiary of Magnetrol of DownersGrove, Ill.), which employs pulse-type ultrasound; this sensor detectssubtle changes in positive and negative air pressure and produces acorresponding passive resistive output signal, which may be routed tothe system controller and/or computer 17. One or more of this type ofsensor may be incorporated into infusion circuit 300 by simply fittingthe sensor around any of the tubing lines of infusion circuit 300; infact, the PRO/Pressure-Occlusion Detector may be a suitable alternativeto pressure syringe 34 of circuit 300. Other types of pressure sensors,for example, similar to those known in the art for blood pressuremonitoring, may be employed in infusion circuit 300.

System 10 may further include sensors to detect fluid levels in eluantreservoir 15 and waste bottle 23. Some examples of such sensors, whichalso employ the aforementioned pulse-type ultrasound, are the DripChamber Liquid Level Sensor and the CLD/Continuous Level Detector (bothavailable from INTROTEK®); alternatively, for example, an HPQ-T pipemounted, self-contained liquid sensor (available from Yamatake SensingControl, Ltd.), or an SL-630 Non-Invasive Disposable/Reusable LevelSwitch (available from Cosense, Inc. of Hauppauge, N.Y.) may be employedto detect the fluid levels. Alternately or in addition, system 10 caninclude additional radiation and/or moisture detection sensors, whichcan detect leaks. With reference to FIG. 1D, such sensors are preferablylocated in proximity to fittings 311, 312, 313, 314 and 315 that joinportions of circuit 300 to one another. Some examples of leak detectionsensors include, without limitation, those in the HPQ-D leak detectionsensor family, and the HPF-D040 fiberoptic leak detector (all availablefrom Yamatake Sensing Control, Ltd.). System 10 may further includeadditional sensors to detect contaminants and/or air bubbles within thetubing lines of circuit; examples of such sensors include the Point-airDetection (PAD) Sensor, that employs pulse-type ultrasound for airbubble detection, and the Blood Component Detector that employs opticalsensing technology to perform Colorimetry-based fluid detection ofunwanted elements in the tubing lines (both available from INTROTEK®).

According to those embodiments that include any of the above sensors,the sensors are linked into the controller of system 10 and/or computer17, either of which may provide a signal to a user of system 10, when aflow anomaly is detected, and/or information to the user, via monitor172, concerning fluid levels, pressure and/or flow through circuit 300.Computer 17 may be pre-programmed to display, for example, on monitor172, a graphic of infusion circuit 300 wherein each zone of the circuit,where an anomaly has been detected, is highlighted, and/or to provideguidance, to the system user, for correcting the anomaly. It should benoted that the alternative infusion circuits illustrated in FIGS. 12A-B,which will be described below, may also include any or all of thesetypes of sensors.

With further reference to FIG. 1D, it may be appreciated that shieldingassembly 200 encloses those portions of circuit 300 from whichradioactive radiation may emanate, with the exception of that portion ofpatient line 305 p, which must extend out from shielding assembly 200 inorder to be coupled to the patient for injection, or in order to becoupled to shielded sample vials, as will be described below. Thus,technical personnel, who operate system 10, are protected from radiationby shielding assembly 200, except at those times when an infusion istaking place, or when quality control tests require collection of eluateinto sample vials. During infusions and quality control test samplecollection, all technical personnel are typically in another room, orotherwise distanced from system 10, in order to avoid exposure toradiation during the infusion, and, according to some preferredembodiments of the present invention, system 10 includes at least onemeans for informing technical personnel that an infusion is about totake place or is taking place. With reference back to FIGS. 1A and 1C,system 10 is shown including a light projector 100, mounted on post 142.According to the illustrated embodiment, projector 100, projects a lightsignal upward, for maximum visibility, when pump 33 is pumping eluantand elution is taking place within generator 21, or at all times whenpump 33 is pumping eluant. According to some embodiments, the lightsignal flashes on and off when the eluate is being diverted fromgenerator 21 into waste bottle 23, and the light signal shines steadilywhen the eluate is being diverted through patient line 305 p, or visaversa. According to other embodiments, a projector 100 shines a lighthaving a first color, to indicate that eluate is being diverted to wastebottle 23, and then shines a light having a second, different color, toindicate that eluate is being directed to patient line 305 p forinfusion. Light projector 100 may further project a more rapidlyflashing light, for example, for approximately five seconds, once a peakbolus of radioactivity is detected in the eluate, to provide furtherinformation to technical personnel. Alternative means of informingtechnical personnel that an infusion is taking place may also beincorporated by system 10, for example, including audible alarms orother types of visible or readable signals that are apparent at adistance from system 10, including in the control room.

It should be noted that, according to alternate embodiments, system 10includes an ‘on board’ dose calibrator for quality control tests, andcircuit 300 is expanded to include elements for an automated collectionof eluate samples for activity measurements, via the on board dosecalibrator. According to a first set of these alternate embodiments, asample collection reservoir is integrated into circuit 300, downstreamof divergence valve 35WP and in communication with tubing line 305P, inorder to receive quality control test samples of eluate, via tubing line305P, and both the reservoir and the dose calibrator are located in aseparate shielded well. According to a second set of these alternateembodiments, waste bottle 23 is configured to receive the qualitycontrol test samples of eluate, via tubing line 305W, and a dosecalibrator is integrated into shielding assembly 200. Quality controlprocedures will be described in greater detail below, in conjunctionwith FIGS. 6-8B.

When maintenance of system 10 requires the emptying waste bottle 23,relatively easy access to waste bottle 23 is provided through opening139 in top surface 131 of shell 13. It should be noted that technicalpersonnel are preferably trained to empty waste bottle 23 at times whenthe eluate, contained in waste bottle 23, has decayed sufficiently toensure that the radioactivity thereof has fallen below a threshold to besafe. Opening 139 is preferably located at an elevation of betweenapproximately 2 feet and approximately 3 feet; for example, opening 139may be at an elevation of approximately 24 inches, with respect to alower surface of platform 113, or at an elevation of approximately 32inches, with respect to a ground surface upon which wheels 121, 122rest. According to the illustrated embodiment, opening 139 is accessedby lifting panel 134; just within opening 139, a shielded lid or door223 (FIG. 2A) may be lifted away from a compartment of shieldingassembly 200 that contains waste bottle 23. With further reference toFIG. 1C, it may be appreciated that opening 137 provides access to otherportions of circuit 300 for additional maintenance procedures, such aschanging out generator 21 and/or other components of circuit 300, aswill be described below.

For those embodiments of system 10 in which automated quality controltests are performed and/or when system 10 is employed for relativelyhigh volume operation, management of waste may become burdensome, eventhough access to waste bottle 23 is greatly facilitated, as describedabove. Thus, in order to facilitate waste management, some embodimentsof system 10 may employ a separation system to separate salts, includingradioactive elements, from water, for example, via evaporation orreverse osmosis. In an evaporation type system, the water component ofthe waste is evaporated, while in a reverse osmosis type system thewater is separated from the salts, and, then, once confirmed to benon-radioactive, via a radiation detector, is piped to a drain.According to some other embodiments, circuit 300 may be configured sothat the waste may be used to purge air from the tubing lines thereofand/or to perform the bypass flush that was described above, preferablyafter the radioactivity of the waste drops below a critical threshold.

FIGS. 1A and 1C further illustrate a pair of relatively shallow externalrecesses 190, which are formed in upper surface 131 of shell 13, forexample, in order to catch any spills from the infusion system; one ofrecesses 190 is shown located in proximity to post, or hanger 141, whichholds reservoir 15, and in proximity to opening 133, through whichtubing line 301 passes. Another recess 192 is shown formed in uppersurface 131; a width and depth of recess 192 may accommodate storage oftechnical documentation associated with infusion system 10, for example,a technical manual and/or maintenance records, or printouts from printer117 (FIG. 1B). With reference to FIG. 1C, upper surface 131 of shell 13is shown to also include additional recesses 101, which are each sizedto hold a shielded test vial, which contains samples from infusionsystem 10, for example, for breakthrough testing and/or calibration,which will be described in greater detail, below. An exemplary test vialshield is shown in FIG. 1E. The test vial shield of FIG. 1E ispreferably formed from Tungsten rather than lead, for example, to reduceexposure to lead, for improved shielding, and to reduce the weight ofthe shield. FIG. 1E illustrates the test vial shield including a handleto simplify manipulation thereof, but alternative configurations of testvial shields have no handle—for these a sling, or strap, may be employedfor handling.

Additional receptacles 180 are shown formed in bin 18, on either side ofa handle 182, which facilitates removal of bin 18 away from shell 13.Technical personnel may, thus, conveniently transport bin 18 to astorage area for a collection of supplies, for example, sharps, gloves,tubing lines, etc. . . . , into one or more receptacles 180 thereof,and/or to a waste container where separate receptacles 180 of bin 18 maybe emptied of waste, such as packaging for the aforementioned supplies,for example, deposited therein during infusion procedures. According tosome embodiments, one or more additional receptacles are formed in oneor more disposal containers, for example, to contain sharps and/orradioactive waste (other than that contained in waste bottle 23), whichmay be integrated into bin 18, or otherwise fitted into, or attached toshell 13, separate from bin 18.

FIG. 2A is a perspective view of shielding assembly 200, according tosome embodiments of the present invention. With reference to FIGS. 1Cand 2A, together, it may be appreciated that opening 137, in uppersurface 131 of shell 13, provides access to a lid or door 221 of asidewall 201 of shielding assembly 200, which sidewall 201 encloses acompartment sized to contain a radioisotope generator of system 10, forexample, generator 21, previously introduced. It should be noted that,according to alternate embodiments, the compartment enclosed by sidewall201 is large enough to hold more than one generator, for example, toincrease system operating efficiency for relatively high volumeoperation. In some of these alternate embodiments, tubing lines 304 and305 are each branched for parallel flow through the multiple generators,in which case divergence valves may be employed to alternate the flowthrough the generators, one at a time. In others of these alternateembodiments, the multiple generators are connected in series betweentubing line 304 and tubing line 305. In addition, a reservoir foraccumulating eluate may be included in circuit 300, downstream of thegenerators and upstream of divergence valve 35WP, in conjunction with asecond pump, in some cases. Embodiments including multiple generatorsand/or an eluate reservoir and second pump can be employed to bettermanage an activity level of each dose, or patient injection, forexample, as described below, in conjunction with FIGS. 12A-B.

According to the embodiment illustrated in FIG. 2A, opening 137 and door221 are located at a lower elevation, for example, with respect toplatform 113, than are opening 139 and lid 223, which provide access tothe compartment being formed by a sidewall 203 of shielding assembly 200to contain waste bottle 23, as previously described. When panel 132 isseparated from shell 13, and door 221 opened, generator 21 may be liftedout from an opening 231 (FIG. 3A) which mates with door 221 of sidewall201. A weight of generator 21, which includes its own shielding, may bebetween approximately 23 and approximately 25 pounds, thus, according tosome preferred embodiments of the present invention, the elevation ofeach of openings 137 and 231, with respect to the lowermost portion ofthe cabinet structure, is between approximately 1 foot and approximately2 feet, in order to facilitate an ergonomic stance for technicalpersonnel to lift generator 21 out from the compartment. According to anexemplary embodiment, when shielding assembly 200 is contained in thecabinet structure of FIG. 1A, openings 137 and 231 are located at anelevation of approximately 12 inches, with respect to the lower surfaceof platform 113, or at an elevation of approximately 19 inches, withrespect to the ground surface upon which wheels 121, 122 rest. FIG. 1Cfurther illustrates access panel 132 including a security lock 138,which mates with a framework 19 of system 10, shown in FIG. 2B, in orderto limit access to generator 21.

FIGS. 1C and 2A further illustrate a lid or a door 225 of anothersidewall 205 (FIG. 3A) of shielding assembly 200, which encloses anothercompartment that is accessible through opening 137 of shell 13, andwhich is located adjacent the compartment enclosed by sidewall 201. Eachof doors 221, 225 are shown being attached by a corresponding hinge H,and another door 227 is shown attached to sidewall 203 by another hingeH. FIG. 2A illustrates each of lid 223 and doors 221, 225, 227 includinga handle 232, 212, 252 and 272, respectively, for moving lid 223 anddoors 221, 225, 227, in order to provide access to the correspondingcompartments, which can be seen in FIGS. 3A-B. FIG. 2A furtherillustrates optional thumb screws 290, one securing lid 223 to sidewall203 and another securing door 221 to sidewall 201, or other means forsecuring the doors, which are known to those skilled in the art, may beincorporated. Each sidewall 201, 203, 205 and the corresponding lid/door223, 221, 225, 227 thereof may be individually cast from 3% antimonylead, or from other known shielding materials, and then assembledtogether according to methods known to those skilled in the art.

According to the illustrated embodiment, doors 221, 225 are hinged toopen in an upward direction, per arrows D and C, and, with referenceback to FIG. 1C, a latch component 191 is provided to hold each of doors221, 225 in an opened position, thereby, preventing doors 221, 225 fromfalling closed, which could pinch/crush fingers of technical personneland/or tubing lines of circuit 300, when in the midst of a maintenanceprocedure. FIG. 2B is a perspective view of framework 19 of the cabinetstructure of system 10, according to some embodiments, to which latchcomponent 191 is mounted; FIG. 2B-1 is an enlarged detailed view oflatch component 191, according to some embodiments. FIG. 2B illustrateslatch component 191 including a first pin 193, corresponding to door225, and a second pin 195, corresponding to door 221; each pin 193, 195includes a lever end 193A, 193B, respectively, and a holding end 193B,195B, respectively. An edge of each door 221, 225, upon opening of doors221, 225, may push past the holding end 195B, 193B of the correspondingpin 195, 193, in a first direction, per arrow F, and then may restagainst a respective side S95 and S93 of each end 195B, 193B, until thecorresponding lever end 195A, 193A is rotated in a counter-clockwisedirection, per arrow cc, thereby moving the corresponding holding end193B, 195B to make way for the closing of doors 221, 225. Doors 221, 225being held by latch component 191 in an open position may be seen inFIG. 3A.

With further reference to FIG. 2A, according to some preferredembodiments of the present invention, an edge of door 225 overlaps door221 to prevent door 221 from being opened, per arrow D, if door 225 isnot opened, per arrow C; and an edge of door 227 overlaps an edge ofdoor 225 to prevent door 225 from being opened if door 227 is notopened, per arrow B; and an edge of lid 223 overlaps door 227 to preventdoor 227 from being opened if lid 223 is not opened, per arrow A. Thus,access to the compartment enclosed by sidewall 201 and containinggenerator 21 is only systematically allowed through a sequential openingof lid 223 and doors 227, 225, 221, since, when generator 21 is replacedit is typically desirable to also replace those portions of circuit 300which are shielded behind lid 223 and doors 227, 225. The routing ofthese portions of circuit 300 will be described in conjunction withFIGS. 3A-C.

FIG. 3A is another perspective view of shielding assembly 200, accordingto some embodiments of the present invention. In FIG. 3A, lid 223 anddoors 221, 225, and 227 are opened to provide a view into openings 233,235 and 231 of sidewalls 203, 205 and 201, respectively, and into apassageway 207, which is formed in sidewall 203, opposite thecompartment, which contains waste bottle 23. Passageway 207 is shownextending vertically along sidewall 203 and having a grooved extension213 formed in a perimeter surface of opening 233. An optional retainingmember 237, for example, formed from an elongate strip of resilientplastic having a generally c-shape cross-section, is shown being mountedalong a length of passageway 207 to hold lines 305 w and 305 p in placewithin passageway 207. FIG. 3A further illustrates a pair of passageways251 b and 251 g, which are formed as grooves in a portion of sidewall205, and another pair of passageways 215 i and 215 o, which are formedas grooves in a portion of sidewall 201. A routing of portions of tubingcircuit 300 (FIG. 1D) through passageways 207, 251 b, 251 c, 215 i and215 o is shown in FIG. 3B.

FIG. 3B illustrates tubing line 304 being routed through passageways 251g and 215 i, eluate tubing line 305 being routed through passageway 215o, and both waste line 305 w and patient line 305 p being routed alongpassageway 207. Waste line 305 w further extends through groovedextension 213 to waste bottle 23, and patient line 305 p further extendsoutward from shielding assembly 200, for example, to extend out throughopening 135 in upper surface 131 of shell 13 (FIG. 1A). According to theillustrated embodiment, each passageway formed in shielding assembly200, by being accessible along a length thereof, can facilitate arelatively easy routing of the corresponding tubing line therethrough,when the corresponding lid/door is open, and a depth of each passagewayprevents pinching and/or crushing of the corresponding tubing linerouted therethrough, when the corresponding lid/door is closed downthereover. With further reference to FIGS. 3A-B, it may be appreciatedthat the compartment formed by sidewall 201 may have a shape matching anexterior contour of generator 21, such that generator 21 is ‘keyed’ tothe compartment, for example, to prevent installation of an impropergenerator into system 10, and/or to facilitate the proper orientation ofgenerator 21 within the compartment for the proper routing of tubinglines. Alternately, or in addition, according to alternate embodiments,if system 10 includes a reader of encoded information in communicationwith computer 17, a unique identification and/or data associated witheach generator may be provided, for example, in a bar code label or aradiofrequency identification (RFID) tag that is attached to eachgenerator, so that the reader may transfer the information to computer17, when a generator is installed, in order to either enable systemoperation or to provide an indication to the user that an incorrectgenerator has been installed. Of course a user of system 10 may,alternately, manually enter information, that is provided on a generatorlabel or marking, into computer 17, in order to either enable system 10,or to receive feedback from computer 17 that the incorrect generator isinstalled.

FIG. 3A further illustrates sidewall 205 including a valve actuatorreceptacle 253, into which divergence valve 35WP is mounted, to becontrolled by one of the servomotors (not shown) of system 10, and anopening 325 for activity detector 25. Activity detector 25 is mounted ina shielded well 255 that extends downward from opening 325 (shown inFIG. 3B), and, with reference to FIG. 3B, tubing line 305 passes overopening 325 so that detector 25 can detect an activity of the eluate,which passes therethrough. According to some embodiments, thepositioning, within the compartment enclosed by sidewall 205, of thecomponents of the portion of infusion circuit 300 which are shown routedtherein, is facilitated by providing the components mounted in a frame39 as a disposable subassembly 390, an embodiment of which isillustrated by FIGS. 3C-D.

FIG. 3C is a perspective view of subassembly 390, and FIG. 3D is aperspective view of frame 39. According to the embodiment illustrated byFIG. 3D, frame 39 is formed from mating trays 39A, 39B, for example,formed from a thermoformed plastic, which fit together to capture,therebetween, and hold, in fixed relation to a perimeter edge of frame39, divergence valve 35WP and portions of eluant tubing line 304,by-pass tubing line 303, eluate tubing line 305, waste line 305 w andpatient line 305 p. FIG. 3C illustrates the perimeter edge divided intoa first side 391, a second side 392, opposite first side 391, a thirdside 393, extending between first and second sides 391, 392, and afourth side 394, opposite third side 393. Although FIG. 3D shows trays39A, 39B individually formed for fitting together, according toalternate embodiments, mating trays of frame 39 may be parts of acontinuous sheet of plastic folded over on itself.

According to the illustrated embodiment, an end 404A, of eluant line304, and an end 403, of by-pass line 303 extend from third side 393 offrame 39 to couple with divergence valve 35BG and an upstream section ofeluant tubing line 302. FIG. 3C further illustrates an opposite end 404Bof eluant line extending from first side 391 of frame 39, alongside asimilarly extending end 405 of eluate line 305, and ends 406 and 407 ofpatient line 305 p and waste line 305 w, respectively, extending fromsecond side 392 of frame 39. Although ends 406, 407 are shown extendingupward from tray 39 a, as they would within shielding assembly 200, itshould be appreciated that the tubing lines of circuit 300 arepreferably flexible and would drop down under their own weight ratherthan extending upward, as shown, if not supported. Referring back toFIG. 1D, in conjunction with FIG. 3C, it can be seen that theaforementioned fittings are provided for coupling subassembly 390 intocircuit 300: first fitting 311 couples the section of eluant line 302 tofilter 37; second fitting 312 couples eluant line 304 to an inlet portof generator 21; third fitting 313, which may incorporate a check valve,couples eluate line 305 to an outlet port of generator 21; fourthfitting 314 couples waste line 305 w to waste bottle 23; and fifthfitting 315 couples patient line 305 p to an extension thereof, whichextends outside shell 13 (designated by the dotted line). Each of thefittings 311, 312, 313, 314, 315 may be of the Luer type, may be a typesuitable for relatively high pressure applications, or may be any othersuitable type that is known to those skilled in the art.

As previously mentioned, when generator 21 is replaced, it is typicallydesirable to also replace those portions of circuit 300 which areshielded behind lid 223 and doors 227, 225, and, in those instanceswherein system 10 is moved to a new site each day, these portions may bereplaced daily. Thus, according to the illustrated embodiment, theseportions are conveniently held together by frame 39, as subassembly 390,in order to facilitate relatively speedy removal and replacement, whileassuring a proper assembly orientation, via registration with featuresformed in sidewall 205 (FIG. 3A), for example: registration ofdivergence valve 35WP with valve actuator receptacle 253, registrationof tubing line ends 403 and 404A with passageways 251 b and 251 g,respectively, registration of tubing line ends 404B and 405 withpassageways 215 i and 215 o, respectively, and registration of tubingline ends 406 and 407 with passageway 207.

With further reference to FIG. 3B, other portions of tubing circuit 300are shown. FIG. 3B illustrates eluant tubing line 301 extending fromreservoir 15, outside of shell 13 (FIG. 1A), to syringe pump 33, whichis mounted to an actuating platform 433. According to the illustratedembodiment, platform 433 is actuated by another servomotor (not shown)of system 10, which is controlled by the controller and computer 17 ofsystem 10, to cause a plunger of pump 33 to move, per arrow I, so as todraw in eluant, from reservoir 15, through tubing line 301, and then tocause the plunger to move in the opposite direction so as to pump theeluant, through tubing line 302, to either generator 21 or to by-passline 303. Although the illustrated embodiment includes syringe pump 33,other suitable pumps, known to those skilled in the art, may besubstituted for pump 33, in order to draw eluant from reservoir 15 andto pump the eluant throughout circuit 300. Although not shown, it shouldbe appreciated that divergence valve 35BG is fitted into another valveactuating receptacle mounted within shell 13 and coupled to yet anotherservomotor (not shown) of system 10.

FIG. 3B further illustrates a filter holder 317 that is mountedalongside an interior surface of shell 13 to hold filter 37 (FIG. 1D) oftubing line 302. Filter holder 317, like frame 39 for subassembly 390,may be formed from a thermoformed plastic sheet; holder 317 may have aclam-shell structure to enclose filter 37 in an interior space, yetallow tubing line 302, on either side of filter 37, to extend out fromthe interior space, in between opposing sides of the clam-shellstructure. Holder 317 is shown including an appendage 307 for hangingholder 317 from a structure (not shown) inside shell 13.

Turning now to FIGS. 4-9C details concerning computer-facilitatedoperation of system 10 will be described, according to some embodimentsof the present invention. As previously mentioned, and with referenceback to FIG. 1A, computer 17 of system 10 includes monitor 172, which,preferably, not only displays indications of system operation to informa user of system 10, but is also configured as a touch screen to receiveinput from the user. It should be understood that computer 17 is coupledto the controller of system 10, which may be mounted within the interiorspace surrounded by shell 13. Although FIG. 1A shows computer 17 mountedto post 142 of system 10, for direct hardwiring to the controller ofsystem 10, according to some alternate embodiments, computer 17 iscoupled to the controller via a flexible lead that allows computer 17 tobe positioned somewhat remotely from those portions of system 10, fromwhich radioactive radiation may emanate; or, according to some otherembodiments, computer 17 is wirelessly coupled, for example, via two-waytelemetry, to the controller of system 10, for even greater flexibilityin positioning computer 17, so that the operation of system 10 may bemonitored and controlled remotely, away from radioactive radiation.

According to some preferred embodiments, computer 17 is pre-programmedto guide the user, via monitor 172, through procedures necessary tomaintain system 10, to perform quality control tests on system 10, andto operate system 10 for patient infusions, as well as to interact withthe user, via the touch-screen capability of monitor 172, according topreferred embodiments, in order to track volumes of eluant and eluatecontained within system 10, to track a time from completion of eachelution performed by system 10, to calculate one or more systemparameters for the quality control tests, and to perform various dataoperations. Computer 17 may also be pre-programmed to interact with thecontroller of system 10 in order to keep a running tally or count ofelutions per unit time, for a given generator employed by the system,and may further categorize each of the counted elutions, for example, asbeing generated either as a sample, for quality control testing, or as adose, for patient injection. The elution count and categorization, alongwith measurements made on each sample or dose, for example, activitylevel, volume, flow rate, etc. . . . , may be maintained in a storedrecord on computer 17. All or a portion of this stored information canbe compiled in a report, to be printed locally, and/or to beelectronically transferred to a remote location, for example, via aninterne connection to technical support personnel, suppliers, serviceproviders, etc. . . . , as previously described. Computer 17 may furtherinteract with the user and/or a reader of encoded information, forexample, a bar code reader or a radiofrequency identification (RFID) tagreader, to store and organize product information collected from productlabels/tags, thereby facilitating inventory control, and/or confirmingthat the proper components, for example, of the tubing circuit, and/oraccessories, and/or solutions are being used in the system.

It should be understood that screen shots shown in FIGS. 4-9C areexemplary in nature and are presented to provide an outline of somemethods of the present invention in which computer 17 facilitates theaforementioned procedures, without limiting the scope of the inventionto any particular computer interface format. Computer 17 may alsoinclude a pre-programmed user manual, which may be viewed on monitor172, either independent of system operation or in conjunction withsystem operation, for example, via pop-up help screens. Although theEnglish language is employed in the screen shots of FIGS. 4-9C, itshould be understood that, according to some embodiments, computer 17 ispre-programmed to provide guidance in multiple languages.

FIG. 4 is a screen shot of a main menu 470, which is presented bycomputer 17 on monitor 172, according to some embodiments. Main menu 470includes a listing of each computer-facilitated operation that may beselected by the user, once the user has logged on. According to somemulti-lingual embodiments, computer 17 presents a list of languages fromwhich the user may select, prior to presenting main menu 470.

FIG. 5A is a schematic showing a series of screen shots which includes alog in screen 570. According to some embodiments, when the usertouch-selects the data entry fields of screen 570 or 571, or of any ofthe other screens presented herein, below, a virtual keyboard isdisplayed for touch-select data entry into the selected data entryfield; alternately, computer 17 may be augmented with another type ofdevice for user data entry, examples of which include, withoutlimitation, a peripheral keyboard device, a storage medium (i.e. disk)reader, a scanner, a bar code reader (or other reader of encodedinformation), a hand control (i.e. mouse, joy stick, etc. . . . ).Although not shown, according to some embodiments, screen 570 mayfurther include another data entry field in which the user is requiredto enter a license key related to the generator employed by system 10 inorder to enable operation of system 10; the key may be time sensitive,related to generator contract terms. Of course any number of log inrequirements may be employed, according to various embodiments, and maybe presented on multiple sequentially appearing screens rather than on asingle log in screen.

After the user enters the appropriate information into data entry fieldsof log in screen 570, computer 17 presents a request for the user toconfirm the volume of eluant that is within reservoir 15 (e.g. saline insaline bag), via a screen 571, and then brings up main menu 470. If theuser determines that the volume of eluant/saline is insufficient, theuser selects a menu item 573, to replace the saline bag. If system 10includes an encoded information reader, such as a bar code or RFID tagreader, confirmation that the selected reservoir is proper, i.e.,contains the proper saline solution, may be carried out by computer 17,prior to connecting the reservoir into circuit 300, by processinginformation read from a label/tag attached to the reservoir.Alternatively, or in addition, tubing line 301 of circuit 300 may beprovided with a connector which only mates with the proper type ofreservoir 15. According to some embodiments, system 10 may furtherinclude an osmolarity or charge detector, which is located justdownstream of reservoir 15 and is linked to computer 17, so that anerror message may be presented on monitor 172 stating that the wrongosmolarity or charge is detected in the eluant supplied by reservoir,indicating an improper solution. One example of a charge detector thatmay be employed by system 10 is the SciCon™ Conductivity Sensor(available from SciLog, Inc. of Middleton, Wis.).

Once the reservoir/saline bag is successfully replaced, computer 17prompts the user to enter a quantity of saline contained by the newsaline bag, via a screen 574. Alternately, if system 10 includes theaforementioned reader, and the saline bag includes a tag by which volumeinformation is provided, the reader may automatically transfer thequantity information to computer 17. Thus, computer 17 uses either theconfirmed eluant/saline volume, via screen 571, or the newly enteredeluant/saline volume as a baseline from which to track depletion ofreservoir volume, via activations of pump 33, in the operation of system10. With reference to FIG. 5B, during the operation of system 10, whencomputer 17 detects that the eluant reservoir/saline bag has beendepleted to a predetermined volume threshold, computer 17 warns theuser, via a screen 577. If the user has disregarded screen 577 andcontinues to deplete the saline bag, computer 17 detects when the salinebag is empty and provides indication of the same to the user, via ascreen 578. To replenish the reservoir/saline bag, the user may eitherrefill the reservoir/bag or replace the empty reservoir/bag with a fullreservoir/bag. According to some embodiments, system 10 automaticallyprecludes any further operation of the system until the reservoir isreplenished. It should be noted that, as previously mentioned, system 10can include a fluid level sensor coupled to the eluant reservoir inorder to detect when the level of saline drops below a certain level.

In addition to tracking the volume of eluant in reservoir 15, computer17 also tracks a volume of the eluate which is discharged from generator21 into waste bottle 23. With reference to FIG. 5C, an item 583 isprovided in main menu 470, to be selected by the user when the userempties waste bottle 23. When the user selects item 583, computer 17presents a screen 584, by which the user may effectively commandcomputer 17 to set a waste bottle level indicator to zero, once the userhas emptied waste bottle 23. Typically, the user, when powering upsystem 10 for operation, each day, will either empty waste bottle 23, orconfirm that waste bottle 23 was emptied at the end of operation theprevious day, and utilize screen 584 to set the waste bottle levelindicator to zero. Thus, computer 17, can track the filling of wastebottle 23 via monitoring of the operation of pump 33 and divergencevalve 35WP, and provide an indication to the user when waste bottle 23needs to be emptied, for example, via presentation of screen 584, inorder to warn the user that, unless emptied, the waste bottle willoverflow. According to some embodiments, system 10 automaticallyprecludes any further operation of the system until the waste bottle isemptied. According to some alternative embodiments, a fluid level sensormay be coupled to waste bottle 23, for example, as mentioned above inconjunction with FIG. 1D, in order to automatically detect when wastebottle 23 is filled to a predetermined level and to provide, viacomputer 17, an indication to the user that waste bottle 23 needs to beemptied and/or to automatically preclude operation of system 10 untilthe waste bottle is emptied.

In addition to the above maintenance steps related to eluant and eluatevolumes of system 10, the user of system 10 will typically performquality control tests each day, prior to any patient infusions. Withreference to FIG. 6, according to preferred methods, prior to performingthe quality control tests (outlined in conjunction with FIGS. 7A-C and8A-B), the user may select an item 675 from main menu 470, in order todirect system 10 to wash the column of generator 21. During thegenerator column wash, which is performed by pumping a predeterminedvolume of eluant, for example, approximately 50 milliliters, throughgenerator 21 and into waste bottle 23, computer 17 provides anindication, via a screen 676, that the wash is in progress. Also, duringthe generator column wash, the system may provide a signal to indicatethat eluate it being diverted to waste bottle 23, for example, lightprojector 100 (FIG. 1C) may project a flashing light signal, aspreviously described.

FIG. 6 further illustrates a screen 677, which is presented by computer17 upon completion of the column wash, and which provides an indicationof a time lapse since the completion of the wash, in terms of a timecountdown, until a subsequent elution process may be effectively carriedout. While screen 677 is displayed, system 10 may be refilling, fromreservoir 15, pump 33, which has a capacity of approximately 55milliliters, according to some embodiments. According to some preferredembodiments of the present invention, computer 17 starts a timer onceany elution process is completed and informs the user of the time lapse,either in terms of the time countdown (screen 677), or in terms of atime from completion of the elution, for example, as will be describedin conjunction with FIG. 7B. According to an exemplary embodiment,wherein generator 21 is the CardioGen-82® that yields a saline solutionof Rubidium-82, produced by the decay of Strontium-82, via the elution,a time required between two effective elution processes is approximately10 minutes.

Once the appropriate amount of time has lapsed, after the elutionprocess of generator column wash, a first quality control test may beperformed. With reference to FIG. 7A, the user may select, from mainmenu 470, an item 773A, which directs computer 17 to begin a sequencefor breakthrough testing. According to some embodiments, in conjunctionwith the selection of item 773A, the user attaches a needle to an end ofpatient line 305 p and inserts the needle into to a test vial, for thecollection of an eluate sample therefrom, and, according to FIG. 7A,computer 17 presents a screen 774, which instructs the user to insertthe test vial into a vial shield, which may be held in recess 101 ofshell 13 (FIG. 1C).

FIG. 7A further illustrates a subsequent screen 775, by which computer17 receives input, from the user, for system 10 to start thebreakthrough elution, followed by a screen 776, which provides both anindication that the elution is in progress and an option for the user toabort the elution. As previously described, the system may provide asignal to indicate that elution is in progress, for example, lightprojector 100 (FIG. 1C) may project a flashing light signal during thatportion of the elution process when eluate is diverted from generator 21through waste line 305 w and into waste bottle 23, and then a steadylight signal during that portion of the elution process when the eluateis diverted from generator 21 through patient line 305 p and into thetest vial, for example, once activity detector 25 detects a dose rate ofapproximately 1.0 mCi/sec in the eluate discharged from generator 21.Another type of light signal, for example, the more rapidly flashinglight, as previously described, may be projected when a peak bolus ofradioactivity is detected in the eluate.

Upon completion of the elution process for breakthrough testing,computer 17 presents a screen 777, shown in FIG. 7B, which, like screen677, provides an indication of a time lapse since the completion of theelution, but now in terms of a time since completion of the breakthroughelution process. When the user transfers the vial containing the sampleof eluate into a dose calibrator, to measure the activity of the sample,the user may make a note of the time lapse indicated on screen 777. Withfurther reference to FIG. 7B, once the user has received the activitymeasure from the dose calibrator, the user proceeds to a screen 778,which includes data entry fields for the activity measure and the timebetween that at which the dose calibrator measured the activity of thesample and that at which the elution was completed. The user may enterthe data via the touch-screen interface of monitor 172, or via any ofthe other aforementioned devices for user data entry. According to somealternate embodiments, computer 17 may receive the data, electronically,from the dose calibrator, either via wireless communication or a cableconnection.

After the data is entered by the user, computer 17 presents screen 779,from which the user moves back to main menu 470 to perform a systemcalibration, for example, as will be described in conjunction with FIGS.8A-B, although the breakthrough testing is not completed. With referenceback to FIG. 7A, an item 773B is shown in main menu 470; item 773B mayonly be effectively selected following the completion of steps for item773A, so as to perform a second stage of breakthrough testing. In thesecond stage, the breakthrough of the sample of eluate collected in thetest vial for the breakthrough testing is measured, at a time ofapproximately 60 minutes from the completion of the elution thatproduced the sample. With reference to FIG. 7C, after the user hasselected item 773B from main menu 470, in order to direct computer 17 toprovide breakthrough test results, a screen 781 is displayed. Screen 781includes, for reference, the values previously entered by the user inscreen 778, along with another pair of data entry fields into which theuser is instructed to enter the breakthrough reading of the sample at 60minutes and the background radiation reading, respectively. After theuser enters this remaining information, as described above, computer 17may calculate and then display, on a screen 782, the breakthrough testresults. According to the illustrated embodiment, computer 17 alsodisplays on screen 782 pre-programmed allowable limits for the results,so that the user may verify that the breakthrough test results are incompliance with acceptable limits, before moving on to a patientinfusion. According to some embodiments, system 10 will not allow aninfusion if the results exceed the acceptable limits, and may present ascreen explaining that the results are outside the acceptable limits;the screen may further direct the user to contact the generatorsupplier, for example, to order a replacement generator.

With reference to FIG. 8A, during the aforementioned 60 minute timeperiod, while waiting to complete the breakthrough testing, the user mayperform calibration by selecting item 873 from main menu 470. Uponselection of item 873, computer 17 presents a screen 874, whichinstructs the user to insert a new test vial into an elution vialshield. In addition to placing the vial in the shield, the user,preferably, replaces patient line 305 p with a new patient line, andthen attaches a needle to the end of the new patient line for insertioninto the test vial, in order to collect an eluate sample therefrom.After performing these steps, the user may move to screen 875, wherein aplurality of data entry fields are presented; all or some of the fieldsmay be filled in with pre-programmed default parameters, which the userhas an option to change, if necessary. Once the user confirms entry ofdesired parameters for the calibration, the user may enter a command,via interaction with a subsequent screen 876, to start the calibrationelution.

With reference to FIG. 8B, after computer 17 starts the elution process,a screen 87 informs the user that the calibration elution is in progressand provides an option to abort the elution. As previously described,the system may provide an indication that elution is in progress, forexample, light projector 100 (FIG. 1C) may project a flashing lightsignal during that portion of the elution process when eluate isdiverted from generator 21 through waste line 305 w and into wastebottle 23, and then a steady light signal during that portion of theelution process when activity detector 25 has detected that a prescribeddose rate threshold is reached, for example, 1.0 mCi/sec, and the eluateis being diverted from generator 21, through the new patient line, andinto the test vial. Another type of light signal, for example, the morerapidly flashing light, as previously described, may be projected when apeak bolus of radioactivity is detected in the eluate. Upon completionof the elution process for calibration, computer 17 presents a screen878, which provides an indication of a time lapse since the completionof the elution, in terms of a time since completion of the calibrationelution process. When the user transfers the vial containing the sampleof eluate into the dose calibrator, to measure the activity of thesample, the user may make a note of the time lapse indicated on screen878. With further reference to FIG. 8B, once the user has received theactivity measure from the dose calibrator, the user proceeds to a screen879, which includes data entry fields for the activity measure and thetime, with respect to the completion of elution, at which the dosecalibrator measured the activity of the sample. Once the data is inputby the user, as described above, the computer calculates a calibrationcoefficient, or ratio, and presents the ratio on a screen 880. Accordingto FIG. 8B, screen 880 further provides an indication of a desirablerange for the calibration ratio and presents an option for the user toreject the calculated ratio, in which case, the user may instructcomputer 17 to recalculate the ratio.

As previously mentioned, some alternate embodiments of the presentinvention include an on board dose calibrator so that the entiresequence of sample collection and calculation steps, which are describedabove, in conjunction with FIGS. 6-8B, for the quality controlprocedures, may be automated. This automated alternative preferablyincludes screen shots, similar to some of those described above, whichprovide a user of the system with information at various stages over thecourse of the automated procedure and that provide the user withopportunities to modify, override and/or abort one or more steps in theprocedure. Regardless of the embodiment (i.e. whether system 10 employsan on board dose calibrator or not), computer 17 may further collect allquality control test parameters and results into a stored record and/orcompile a report including all or some of the parameters and results forlocal print out and/or electronic transfer to a remote location.

With reference to FIG. 9A, upon completion of the above-describedquality control tests, the user may select an item 971, from main menu470, in order to direct system 10 to begin a procedure for thegeneration and automatic infusion of a radiopharmaceutical into apatient. As previously described, system 10 infuses the patient with theradiopharmaceutical so that nuclear diagnostic imaging equipment, forexample, a PET scanner, can create images of an organ of the patient,which absorbs the radiopharmaceutical, via detection of radioactiveradiation therefrom. According to FIG. 9A, upon selection of item 971,computer 17 presents a screen 972 which includes a data entry field fora patient identification number. This identification number that isentered by the user is retained by computer 17, in conjunction with thepertinent system parameters associated with the patient's infusion.After the user enters the patient identification number, computer 17directs, per a screen 973, the user to attach a new patient line and topurge the patient line of air. A subsequent screen 974 presented bycomputer 17 includes data entry fields by which the user may establishparameters for the automatic infusion; all or some of the fields may befilled in with pre-programmed default parameters, which the user has anoption to change, if necessary.

With reference to FIG. 9B, if pump 33 does not contain enougheluant/saline for the patient infusion, computer 17 will present awarning, via a screen 901, which includes an option for the user todirect the refilling of pump 33, via a subsequent screen 902. Once pump33 has been filled, computer 17 presents an indication to the user, viaa screen 903. According to some embodiments, if the user does notre-fill pump 33, yet attempts to proceed with an infusion, system 10will preclude the infusion and present another screen, that communicatesto the user that no infusion is possible, if the pump is not refilled,and asking the user to refill the pump, as in screen 901. When pump 33contains a sufficient volume of eluant for the patient infusion,computer 17 presents a screen 975, which is shown in FIG. 9C, and allowsthe user to enter a command for system 10 to start the patient infusion.During the infusion, computer 17 provides the user with an indicationthat the infusion is in process and with an option for the user to abortthe infusion, via a screen 976. As previously described, the system mayprovide an indication that an elution is in progress, for example, lightprojector 100 (FIG. 1C) may project a flashing light signal during thatportion of the elution process when eluate is diverted from generator 21through waste line 305 w and into waste bottle 23, and then a steadylight signal during that portion of the elution process when activitydetector 25 has detected that a prescribed dose rate threshold isreached, for example, 1.0 mCi/sec, and the eluate is being diverted fromgenerator 21, through the new patient line for infusion into thepatient. Another type of light signal, for example, the more rapidlyflashing light, previously described, may be projected when a peak bolusof radioactivity is detected in the eluate. At the completion of theinfusion, a screen 977 is displayed by computer 17 to inform the user ofthe completion of the infusion and a time since the completion. Computer17 also displays a summary of the infusion, per screen 978.

With further reference to FIG. 9C, screen 976 shows an exemplaryactivity profile (activity—mCi/sec, on y-axis, versus time—sec, onx-axis) for the infusion/injected dose (designated between the twovertical lines). Those skilled in the art will appreciate that the shapeof this profile depends upon the infusion flow rate, for a given volumeof the dose, which flow rate is controlled, for example, by the speed atwhich pump 33 drives flow through the patient line, and upon the amountof Strontium-82 remaining in the generator. In the absence of flow ratecontrol, activity profiles may change over the life of the generator.Furthermore, the peak bolus of radioactivity, particularly for injecteddoses from a relatively new generator, may exceed a saturation level ofthe imaging equipment, i.e. PET scanner. According to some preferredmethods of the present invention, in order to maintain relativelyconsistent, and desirable/effective, activity profiles for patientinjections, over the life of the generator, the operating speed of pump33 may be varied (both over the course of a single injection and frominjection to injection), according to feedback from activity detector25. Such a method may be implemented via incorporation of anotherquality control test in which pump 33 is operated to drive flow throughthe generator at a constant rate, in order to collect, into computer, aplurality of activity measurements from activity detector 25; theplurality of measurements comprise a characteristic, or baselineactivity profile from which the computer 17 may calculate an appropriateflow rate profile to control a speed of pump 33, in order to achieve thedesirable/effective activity profile. In general, at the start ofgenerator life, when Strontium-82 is plentiful, the pump is controlledto drive infusion flow at relatively lower rates, and, then, toward theend of generator life, when much of the Strontium-82 has been depleted,the pump is controlled to drive infusion flow at relatively higherrates. As was described above, in conjunction with FIG. 1D, if a desiredinfusion/injection flow rate is relatively high, that is, high enough tocreate too much back pressure, via flow through the column of generator21, by-pass line 303 may be employed by adjusting divergence valve 35BGto divert a flow of eluant therethrough after a sufficient volume hasbeen pumped through generator at a lower flow rate. According to thismethod, once a dose of eluate, from generator 21, has flowed intopatient line 305 p, divergence valve 35BG is set to divert the flow ofeluant through by-pass line 303, and then pump speed is increased topump eluant at a higher flow rate in order to push the dose out frompatient line 305 p, for injection at the higher flow rate.

Consistency of activity profiles among injected doses can greatlyfacilitate the use of PET scanning for the quantification of flow, forexample, in coronary perfusion studies. Alternative infusion circuitconfigurations, operable according to alternative methods, to achieveconsistency of activity profiles among injected doses, as well as a moreuniform level of radioactivity across each individual dose, will bedescribed below, in conjunction with FIGS. 12A-C.

Printer 117 (FIG. 1B) may be activated to print out a hard copy of theinfusion summary, on which the patient identification number andpertinent infusion and system parameters are also printed, forreference. Alternatively, or in addition, according to some embodiments,the summary may be downloaded onto a computer readable storage device tobe electronically transferred to one or more remote computers and/or thesummary may be automatically transferred to the one or more remotecomputers, via wireless communication or a cable connection, forexample, over an intranet network and/or the internet. In order toprotect private patient information, the files may be encrypted fortransmission over the internet. The one or more remote computers may beincluded, for example, in a hospital information system, and/or abilling system, and/or in a medical imaging system. Infusion parameters,for example, corresponding to the activity profile, may also becollected and electronically transferred for analysis in conjunctionwith captured images, for example, in order to quantify coronary flow,via a software package that is loaded into a system that includes thePET scanner.

With reference back to FIG. 9A the user may select an item 995, frommain menu 470, in order have system 10 perform data operations, such as,archiving a data base of patient infusion information and qualitycontrol test results, transmitting patient infusion summary records toUSB mass storage devices, and various types of data filtering, forexample, according to date ranges and/or patient identification numbers,for example, to search for a particular set of data and/or to compile asummary report of related sets of data. Additionally, certaininformation, which is collected by computer 17 over the course of systemoperation, and which defines system operation, may be transmitted to alocal or remote computerized inventory system and/or to computers oftechnical support personnel, maintenance/service providers and/orsuppliers of infusion circuit elements/components, thereby facilitatingmore efficient system operation and maintenance.

Turning now to FIG. 10, an item 981 for computer-facilitated purging ofthe tubing lines of system 10 is shown included in main menu 470. When auser selects item 981, computer 17 guides the user to select either anair purge or a saline purge. The direction provided by computer 17 isnot explicitly laid out herein, for a saline purge, as procedures forsaline purging should be readily apparent to those skilled in the art,with reference to the schematic of infusion circuit 300 shown in FIG.1D. A saline purge of circuit 300 is desired to assure that all the airis removed from circuit 300 when a new generator and/or a new completeor partial tubing set is installed. An air purge of the tubing lines ofcircuit 300 may be performed after removing reservoir 15, by-passinggenerator 21, by connecting tubing line 304 to tubing line 305, andcoupling patient line 305 p to a vial, for example, as is directed bythe computer interface, in screens 983 and 984 shown in FIG. 10. The airpurge is desirable for blowing out the tubing lines, thereby removingall remaining eluant and eluate, prior to installing a new generatorand/or prior to transporting system 10 from one site to another. Ifgenerator 21 is not depleted and will be used in system 10 at the newsite, it is important to by-pass the generator prior to purging thetubing lines of circuit 300 with air, so that air is not blown acrossthe generator, since air through generator 21 may compromise both thefunction and the aseptic nature of generator 21.

According to preferred embodiments, once the user has followed theinstructions presented in screens 983 and 984 and selects to start theair purge, for example, via screen 985, computer 17 directs thecontroller of system 10 to carry out a complete air purge, in which pump33 and divergence valves 35BG and 35WP are automatically controlled. Theautomated air purge preferably includes the following steps, which maybe best understood with reference to tubing circuit 300 in FIG. 1D:pumping any remaining volume of eluant left in pump 33, through lines302, 304, 305 and 305 w, to waste bottle 23; refilling pump 33 with airand pumping the air through lines 302, 304, 305 and 305 w, into wastebottle 23 (lines 304 and 305 have been previously connected directly toone another, in order to by-pass generator 21; if generator 21 isdepleted and will be replaced with a new generator, pumping air throughgenerator 21 may be acceptable); refilling pump 33 with air and thenpumping a portion of the air through lines 302, 304, 305 and 305 p, intothe vial, and then a remaining portion of the air through lines 302,304, 303 and 305 p, into the vial. With reference to FIG. 1D and theprevious description of divergence valves 35BG, 35WP, it should beunderstood how divergence valves 35BG, 35WP are automatically controlledto carry out the above steps.

The purge operations, which are facilitated by selecting item 981 frommain menu 470, may also be accessed via the selection of an item 991 forgenerator setup. When the user selects item 991, computer 17 may presentan option for guidance in removing an old, depleted, generator and a setof tubing lines, prior to installing the new generator, or an option tojust be guided in the installation of the new generator. According tosome embodiments, computer 17 is pre-programmed to calculate an amountof activity left in a depleted generator, for example, by trackingactivity of eluate over a life of the generator. At an end of the lifeof the generator, computer 17 may further compile this information,along with other pertinent generator information, into a report that mayaccompany a declaration of dangerous goods for shipping the depletedgenerator out for disposal or, in some cases, back to the manufacturerfor investigation. An example of such a report is shown in FIG. 11.According to those embodiments of system 10 that include an encodedinformation reader, computer 17 may confirm that the new generator isproper by processing information that is read from an encoded label/tagattached thereto.

FIGS. 12A-B are schematics of alternative infusion circuits 1300A, 1300Bthat may be employed by system 10, in place of circuit 300 (FIG. 1D),according to some additional embodiments of the present invention.Circuits 1300A, 1300B are configured to allow for alternative methods ofoperation, to that previously described for circuit 300, when arelatively even, or uniform level of activity over each injected dose,along with the relatively consistent level of activity from injection toinjection is desired, for example, in order to facilitate aquantification of coronary artery blood flow via PET scanning. FIG. 12Cis a schematic illustrating activity profiles 1200A, 1200B for twoinjected doses, wherein profile 1200B has a more uniform level ofactivity than profile 1200A; profile 1200B may be achieved via theoperation of circuits 1300A, 1300B as described below.

Similar to circuit 300 (FIG. 1D), dashed lines are shown in each ofFIGS. 12A-B to indicate a general boundary of a shielding assembly forportions of each circuit 1300A, 1300B. The shielding assembly for eachof circuits 1300A, 1300B may be very similar, in most respects, toshielding assembly 200, which is described above for system 10, and theelements of each of circuits 1300A, 1300B may be arranged with respectto their respective shielding and with respect to shell 13 of system 10in a similar manner to that described above for circuit 300.

FIG. 12A illustrates circuit 1300A including, like the previouslydescribed circuit 300, eluant reservoir 15, pump 33, radioisotopegenerator 21, through which the filtered eluant is pumped to create theradioactive eluate, activity detector 25, and waste bottle 23. FIG. 12Afurther illustrates two filters 37 and two pressure transducers 1334included in circuit 1300A. Circuit 1300A further includes by-pass tubingline 303, which is located downstream of divergence valve 35BG, like incircuit 300, and which accommodates the previously describedeluant/saline flush. However, in contrast to circuit 300, circuit 1300Afurther includes a linear/proportional valve 1335 integrated intoby-pass/flush line 303 so that circuit 1300A may be operated, forexample, according to pre-programmed parameters of computer 17, inconjunction with feedback of information from activity detector 25, fora controlled by-pass of generator 21 in order to mix eluant with eluateand, thereby, achieve a relatively uniform level of activity over eachpatient injection, for example, according to profile 1200B of FIG. 12C.It should be noted that, in addition to the controlled mixing, a flowrate of each injection may be varied, if necessary, in order to maintaina consistent activity level.

FIG. 12B illustrates circuit 1300B including, like the previouslydescribed circuit 300, eluant reservoir 15, pump 33, radioisotopegenerator 21, activity detector 25, and waste bottle 23, as well as thetwo filters 37 and two pressure transducers 1334, as in circuit 1300A.In contrast to circuits 300 and 1300A, circuit 1300B further includes aneluate reservoir 1350, which is shown located downstream of generator21, in between first and second segments 305A, 305B of the eluate tubingline. It should be noted that a pump is combined with reservoir 1350,for example, similar to syringe pump 33, such that, when a divergencevalve 1335IO is set to allow fluid communication between reservoir 1350and tubing line segment 305A, the associated pump may be operated todraw in a volume of eluate, and, then, when divergence valve 1335IO isset to allow fluid communication between reservoir 1350 and tubing linesegment 305B, the pump may be operated to push the volume of eluate outthrough tubing line segment 305B for a patient injection, whendivergence valve 35WP is set to direct flow into patient line 305 p.With reference back to FIGS. 3A-B, sidewall 205 of shielding assembly200 may be enlarged to further enclose eluate reservoir 1350. Forexample, another shielded well, to house the eluate reservoir, mayextend alongside well 255, in which activity detector 25 is described asbeing mounted. Furthermore, sidewall 205 may include another valveactuator receptacle for divergence valve 1335IO, similar to receptacle253, shown in FIG. 3A for divergence valve 35WP.

Collection of discrete volumes of eluate, in reservoir 1350, may help toachieve a more uniform activity level over each injection, for example,like that of profile 1200B in FIG. 12C, and, according to preferredmethods, feedback from activity detector 25 may be used to control thepump associated with reservoir 1350, in order to vary injection flowrate and, thereby, maintain a relatively consistent activity levelacross multiple injections, and, when necessary, to vary injection flowrate over an individual injection to maintain the uniform activitylevel. Feedback from the pressure transducer 1334, that is downstreamfrom detector 25, and/or from a flow meter (not shown) of circuit 1300Bmay also be used to control the varying of injection flow rate.

With further reference to FIGS. 12A-B, it should be noted thatalternative circuits may be configured to employ a combination of themethods described for circuits 1300A and 1300B. Furthermore, someinfusion circuits of the present invention may employ multiplegenerators 21, as mentioned above, in conjunction with FIG. 2A, to helpmaintain the relatively uniform level of activity over each injectionand the relatively consistent level of activity from injection toinjection.

In the foregoing detailed description, the invention has been describedwith reference to specific embodiments. However, it may be appreciatedthat various modifications and changes can be made without departingfrom the scope of the invention as set forth in the appended claims.

1. An infusion system on-board a cart comprising: a first shielding compartment having a first opening facing vertically upwardly through which a strontium-rubidium radioisotope generator can be inserted into and removed from the first shielding compartment; a first door configured to provide access to the first shielding compartment and to close over the first opening; a second shielding compartment having a second opening facing vertically upwardly through which the waste bottle can be inserted into and removed from the second shielding compartment; wherein the first opening is located at a lower elevation than the second opening; a radioactivity detector positioned to measure radioactivity of a rubidium radioactive eluate flowing through an eluate tubing line in fluid communication with an outlet tubing port of the strontium-rubidium radioisotope generator; a computer configured to receive an input from a user for controlling operation of the infusion system; a shielded well configured to receive an eluate reservoir, wherein the eluate reservoir is configured to receive a test sample; and wherein the computer of the infusion system is configured to: pump saline from a saline reservoir into the strontium-rubidium radioisotope generator through an inlet tubing port of the strontium-rubidium radioisotope generator thereby generating the rubidium radioactive eluate that is discharged through the outlet tubing port, fill the eluate reservoir in the shielded well with the test sample, and determine a strontium breakthrough test result on the test sample filled into the eluate reservoir in the shielded well while the eluate reservoir remains in the shielded well. 